In addition to essential nutrients such as lactose lipids and proteins, human milk contains a large concentration of oligosaccharides. Human milk oligosaccharides (HMO) are complex and diverse molecules. These molecules are composed of glucose (Glc), galactose (Gal), N-acetylglucosamine (GlcNAc), and often contain fucose (Fuc) and/or N-acetylneuraminic acid (NeuAc), linked via several glycosidic bonds. The simplest oligosaccharides in human milk are trisaccharides where lactose can be sialylated to form sialyllactose, or fucosylated to form fucosyllactose. More complex HMO are also based on a lactose core that is conjugated with repeats of lacto-N-biose I (Galβ1-3GlcNAc; LNB; type-1 chain) or N-acetyllactosamine (Galβ1-4GlcNAc; type-2 chain), producing molecules with a degree of polymerization larger than 4 (Bode et al. (2012) Adv. Nutr. 3:383 S). These core structures can be modified by fucose and sialic acid residues via different linkages (De Leoz et al. (2012) J. Proteome Res. 11:4662). Although a large number of different HMO structures have been determined, a few isomers can represent up to 70% of the total molecules.
Remarkably, the energetic value of HMO for the infant is minimal. HMO are resistant to enzymatic hydrolysis from intestinal brush border membrane and pancreatic juices, and therefore the majority of these molecules transit the intestinal tract reaching the colon in intact form. During their transit HMO are believed to prevent pathoge colonization, by serving as decoy binding sites for epithelial glycans (Newburg et al. (2005) Annu Rev. Nutr. 25:37).
Human milk oligosaccharides (HMO) influence the composition of the intestinal microbiota in the first years of life. While the microbial community in breast-fed infants is largely dominated by the genus Bifidobacterium, formula-fed infants show increased bacterial diversity (Roger et al. (2010) Microbiol. 156:3329; Yatsunenko et al. (2012) Nature 486:222). This indicates that both pro- and antimicrobial elements in breast-milk account for these differences. A conceptual basis for co-evolution between bifidobacteria and milk glycans is supported by recent definition of the molecular mechanisms by which these microbes catabolize HMO. In Bifidobacterium longum subsp. infantis (B. infantis) ATCC 15697, these mechanisms include oligosaccharide transporters and intracellular glycosyl hydrolases (GH) such as fucosidases, hexosaminidases and sialidases (Gamido et al. (2012) Adv. Nutr. 3:415 S).